Rippe Catarina, Rippe Anna, Torffvit Ole, Rippe Bengt
Department of Nephrology, Clinical Sciences, Lund University, Lund, Sweden.
Am J Physiol Renal Physiol. 2007 Nov;293(5):F1533-8. doi: 10.1152/ajprenal.00271.2007. Epub 2007 Aug 15.
Microalbuminuria is an early sign of diabetic nephropathy. The aim of the present study was to investigate whether the changes of the glomerular filtration barrier in early experimental diabetes are due to size- or charge-selective alterations. Wistar rats, made diabetic by streptozotocin (STZ) and having their blood glucose maintained at approximately 20 mM for 3 or 9 wk, were compared with age-matched controls. Glomerular clearances of native albumin (Cl-HSA) and neutralized albumin (Cl-nHSA) were assessed using a renal uptake technique. Glomerular filtration rate and renal plasma flow were assessed using (51)Cr-EDTA and [125I]iodohippurate, respectively. In a separate set of animals, diabetic for 9 wk, and in controls, glomerular sieving coefficients (theta) for neutral FITC-Ficoll (molecular radius: 15-90 A) were assessed using size exclusion chromatography. At 3 wk of diabetes, Cl-HSA and Cl-nHSA remained unchanged, indicating no alteration in either size or charge selectivity. By contrast, at 9 wk of diabetes, there was a twofold increase of Cl-HSA, whereas Cl-nHSA remained largely unchanged, at first suggesting a glomerular charge defect. However, according to a two-pore model, the number of large pores, assessed from both Ficoll and Cl-HSA, increased twofold. In addition, a small reduction in proximal tubular reabsorption was observed at 3 wk, which was further reduced at 9 wk. In conclusion, no functional changes were observed in the glomerular filtration barrier at 3 wk of STZ-induced diabetes, whereas at 9 wk there was a decrease in size selectivity due to an increased number of large glomerular pores.
微量白蛋白尿是糖尿病肾病的早期迹象。本研究的目的是调查早期实验性糖尿病中肾小球滤过屏障的变化是由于大小选择性还是电荷选择性改变所致。将经链脲佐菌素（STZ）诱导糖尿病并使其血糖在约20 mM维持3周或9周的Wistar大鼠与年龄匹配的对照组进行比较。使用肾脏摄取技术评估天然白蛋白（Cl-HSA）和中和白蛋白（Cl-nHSA）的肾小球清除率。分别使用（51）Cr-EDTA和[125I]碘马尿酸评估肾小球滤过率和肾血浆流量。在另一组动物中，对糖尿病9周的动物和对照组，使用尺寸排阻色谱法评估中性异硫氰酸荧光素-菲可（FITC-Ficoll，分子半径：15-90 Å）的肾小球筛分系数（θ）。糖尿病3周时，Cl-HSA和Cl-nHSA保持不变，表明大小选择性或电荷选择性均无改变。相比之下，糖尿病9周时，Cl-HSA增加了两倍，而Cl-nHSA基本保持不变，最初提示存在肾小球电荷缺陷。然而，根据双孔模型，从菲可和Cl-HSA评估的大孔数量增加了两倍。此外，在3周时观察到近端肾小管重吸收略有减少，在9周时进一步减少。总之，在STZ诱导的糖尿病3周时，肾小球滤过屏障未观察到功能变化，而在9周时，由于肾小球大孔数量增加，大小选择性降低。
